Post-vaccinial encephalitis and disseminated vaccinia are major concerns with the use of vaccinia virus recombinants as immunization vectors in man. However, because of the efficacy of vaccinia virus recombinants, this virus is still being evaluated in a number of laboratories as a potential live vaccine vector against a wide variety of both human and animal pathogens. Its potential as a vaccine is evident because of its successful employment in the worldwide eradication of Smallpox. Since that time, there have been published a number of studies demonstrating the suitability of the virus as a vector for the delivery and expression of foreign antigens. Since these foreign antigens behave as would a gene of the vaccinia vector itself, a significant immune response and subsequent protection against the antigen, and therefore the infectious agent of interest, would occur simultaneously with the mounting of an immune response against the vaccinia virus vector itself (Piccini, A., and E. Paoletti [1986] "The use of vaccinia virus for the construction of recombinant vaccines," Bioessays, 5:248,252.). Based on past experience, there are questions concerning both the safety and the occasional complications (such as spreading and growth in the brain and nervous system) that can arise from the use of vaccinia as a vaccine. Therefore, if vaccinia virus is to be widely used as a vaccine vector for wide scale human or animal use, efforts to design attenuated strains of virus exhibiting a lesser degree of intrinsic virulence must be undertaken (Brown, F., G. C. Schild, and G. L. Ada [1986] "Recombinant vaccinia viruses as vaccines," Nature 319:549-550).
Over the past 4 or 5 years, there has been a tremendous interest in the possibility of live vaccine vectors and the specific use of vaccinia virus. Vaccinia virus is a known entity, and has received endorsement from the World Health Organization (WHO) for this purpose. One overwhelming reason for this endorsement is the fact that the "cold chain" can be broken. Vaccinia based vaccines do not require refrigeration and can be administered in the field by non-skilled personnel. The market is world-wide, and the technology described here is suitable for both human and animal vaccines.
The commercial possibilities are enormous. The use of vaccinia virus based vaccine technology is appropriate for both human and animal vaccines. Each vaccine construct will have to undergo rigorous testing before endorsement and thereafter periodic testing during production. A simple test system which allows both predictions as to relative virulence coupled with the possibility of custom designing each and every vaccine would facilitate the overall process tremendously and fill a niche in the field which is currently overlooked. The invention described herein accomplishes these highly desirable goals.